Effects Of Regulating Toll-Like Receptor4on The Progression Of Atherosclerosis In ApoE-knockout Mice

Objective:to explore effects of regulating toll-like receptor4with LPS andcurcumin on the progression of atherosclerosis in ApoE-knockoutmice.Methods:82male ApoE-knockout mice were fed a western high-fat dietfrom6weeks of age to12weeks of age.2male ApoE-knockout mice whoseaorta were separated for Hematoxylin-eosin staining verifying thatatherosclerosis plagues appeared and that models of atherosclerosis were successfully built were euthanized randomly at12th weekend.The rest of ApoE-knockout mice were randomly divided into control group l(n=20),control group2(n=20),Cur group(n=20),and LPS group(n=20). Mice were treated with LPS (40microg/per) and vehicle of NS by intraperitoneal injections weekly in the LPS group.And mice were treated with curcumin(20mg/kg) and vehicle of CMCS by gavage every day in Cur group.Mice were regulated with equal volume of vehicle by the same way with LPS group in control group l.And mice were received equal volume of vehicle by the same way with Cur group in control group2.Meanwhile,the same diet as ever for animals continued.After12weeks all ApoE-knockout mice were surgically anesthetized by intraperitoneal injection.And their aortas, brachiocephalic arteries and left subclavian arteries were separated. Areas of atherosclerotic lesions were determined by hematoxylin-eosin staining.Lipid contents of atherosclerosis plaques were assayed by oil red O staining.The protein expression of toll-like receptor4was quantified by western blotting and immunohistochemistry. The change of expression of TLR4mRNA was detected by RT-PCR.Results:1.There were no significant changes between control group1and control group2in TLR4mRNA expressions, also in TLR4protein expressions,plaque areas,and plaque lipid contents (p>0.05).2. Compared with control groups,the expressions of TLR4mRNA and protein significantly decreased(p<0.05).The same changes were observed in the plaque areas and the plaque lipid contents(p<0.05) in Cur group.3.Compared with control groups, the expressions of TLR4mRNA and protein apparently increased(p<0.05).The same changes were observed in the plaque areas and the plaque lipid contents(p<0.05) in LPS group.Conclusion:lnducing the toll-like receptor4may elevate the expressions of TLR4mRNA and protein,and promote the progression of atherosclerosis.Inhibiting the toll-like receptor4may decrease the expressions of TLR4mRNA and protein,and extenuate the progression of atherosclerosis.The results indicat that TLR4may become a treatment target of atherosclerosis.